Glaucoma, a pathologic state in which intraocular pressure exceeding the normal range of 10-20 mmHg results in eyesight disorder, is among the intractable ophthalmopathies. The current therapy for glaucoma is to lower intraocular pressure. For glaucoma chemotherapy, choline agonists, represented by pilocarpine, and anti-choline esterase agents have long been used as eyedrops. These drugs, however, cause severe side effects such as a sensation of darkness due to miosis, eye injection and other symptoms, as well as iridic cystoma, iris synechia, cataract and retinal detachment when used in long-term continuous administration. Although sympathetic nerve agonists such as epinephrine and dipivefrine have been used for their ocular hypotensive action, their use is limited to open-angle glaucoma, and can cause mydriasis, blepharitis and conjunctival pigmentation, and systemic symptoms such as increased heart rate and hypertension. In recent years, .beta.-blockers such as timolol, pindolol and carteolol have been widely used, since they are advantageous in that their instillation suppresses aqueous humor production and lowers ocular tension, without acting on the pupil. These drugs, however, tend to cause local symptoms such as feeling of eye dryness, allergic blepharitis and superficial keratitis. The only group of ocular hypotensive agents that can be used systemically in long-term continuous administration is carbonic anhydrase inhibitors such as acetazolamide and metazolamide, but these can cause gastrointestinal disorder, ureteroliths and electrolytic anomalies. In recent years, angiotensinconverting enzyme inhibitors, which inhibit the reninangiotensin system involved in blood pressure regulation, and angiotensin II antagonists have been reported to be useful as glaucoma remedies, but none have seen practical application.
Recently, ketanserin, which selectively blocks a serotonin (5-HT.sub.2) receptor and is represented by the formula ##STR2## has been reported to simultaneously lower intraocular pressure of both eyes when administered to one eye [JOURNAL OF OCULAR PHARMACOLOGY, Vol. 3, No. 4, pp 279-291 (1987)].
EP-A-145494 and U.S. Pat. No. 4751316 teach that a compound having a completely different chemical structure from ketanserin, which is represented by the formula ##STR3## wherein R.sup.1 and R.sup.2 are each hydrogen, halogen, hydroxyl, lower alkyl or lower alkoxy, R.sup.3 and R.sup.4 are each hydrogen, optionally substituted lower alkyl, optionally substituted cycloalkyl or optionally substituted aralkyl, or form, together with the adjacent nitrogen atom, an optionally substituted ring, X is hydrogen, optionally substituted lower alkyl, optionally substituted aryl or optionally esterified or amidized carboxyl, Y is&gt;C.dbd.O or &gt;CH--OR.sup.5 wherein R.sup.5 is hydrogen, acyl or optionally substituted carbamoyl, m is an integer of from 0 to 2, and n is an integer of from 1 to 6, and a salt thereof have superior serotonin S.sub.2 receptor blocking action, calcium antagonistic action, cerebrovascular contraction remisslye action, renal circulation improving action, diuretic action and antithrombogenic action and are useful for the prevention and treatment of ischemic heart diseases such as angina pestoris and cardiac infarction, thrombus, hypertension, and cerebrocircular disorders such as cerebrovascular contraction and transient ischemic attack. However, no ophthalmic action, particularly local ophthalmic action, of these compounds has been reported.
When developing an ophthalmic agent, attention should be paid to the manifestation of efficacy only in the instillation site, which avoids passage through the systemic circulatory system or the central nervous system, namely, exertion of local action, and it is desirable that the agent does not exert influences on any other part besides the target lesion, or systemic influences. Accordingly, there is a demand for the development of an ophthalmic agent which has a local action, causes less side effects, and can be used safely.